Morbidity in schistosome-infected individuals is caused mainly by the immune response of the host to schistosome eggs deposited in the tissues. In chronic schistosomiasis, fibrotic sequelae to the inflammatory reaction to the eggs are responsible for most clinical disease. Hepatic fibrosis and the granulomatous response to eggs of schistosome species pathogenic for man are studied in mice in relation to parasitologic parameters of infection. Cytokines play an important role in the genesis and regulation of the size of circumoval granulomas and in the fibrosis associated with them. Anti-IL-4 treatment of S. mansoni or S. japonicum-infected mice resulted in a slight decrease in granuloma size, but a major decrease in hepatic fibrosis and a considerable decrease in Th2-type cytokine secretion (IL-4 and IL-5) and an increase in Th1-type cytokines (IFN-gamma and IL-2). Cytokine mRNA was similarly affected. Decreased fibrosis may be caused by decreased IL-4 levels "directly" or perhaps is otherwise related to the decreased Th2 response. Vaccination of mice with S. mansoni eggs together with IL-12 shifted the cytokine response from a predominantly Th2 to a more Th1-like pattern and also reduced hepatic fibrosis dramatically while having a lesser effect on the granulomatous response. The reaction to schistosome eggs has long been considered to be stage specific, i.e., the reaction to schistosome eggs was found not to be affected by previous exposure to antigens of adult worms or larvae. We have found that infection with adult male or female worms separately sensitizes fully for granuloma formation around schistosome eggs.